NM_130806.5:c.95-178G>A

Variant names:

• chr13-31758080-G-A
• rs9594382
• NM_130806.5:c.95-178G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_130806.5(RXFP2):​c.95-178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,946 control chromosomes in the GnomAD database, including 8,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8877 hom., cov: 32)
• Consequence: RXFP2 NM_130806.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.92
• Publications: 1 publications found

Genes affected

RXFP2 (HGNC:17318): (relaxin family peptide receptor 2) This gene encodes a member of the GPCR (G protein-coupled, 7-transmembrane receptor) family. Mutations in this gene are associated with cryptorchidism. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

RXFP2 Gene-Disease associations (from GenCC):

• cryptorchidism

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 13-31758080-G-A is Benign according to our data. Variant chr13-31758080-G-A is described in ClinVar as [Benign]. Clinvar id is 1294621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RXFP2	NM_130806.5	c.95-178G>A		intron_variant	Intron 1 of 17	ENST00000298386.7	NP_570718.1
RXFP2	NM_001166058.2	c.95-178G>A		intron_variant	Intron 1 of 16		NP_001159530.1
RXFP2	XM_017020389.2	c.95-178G>A		intron_variant	Intron 1 of 14		XP_016875878.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP2	ENST00000298386.7	c.95-178G>A		intron_variant	Intron 1 of 17	1	NM_130806.5	ENSP00000298386.2
RXFP2	ENST00000380314.2	c.95-178G>A		intron_variant	Intron 1 of 16	1		ENSP00000369670.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48935 AN: 151830 Hom.: 8875 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.331

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48942 AN: 151946 Hom.: 8877 Cov.: 32 AF XY: 0.325 AC XY: 24159 AN XY: 74270

African (AFR) AF: 0.152 AC: 6282 AN: 41418

American (AMR) AF: 0.428 AC: 6532 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3464

East Asian (EAS) AF: 0.187 AC: 965 AN: 5162

South Asian (SAS) AF: 0.307 AC: 1477 AN: 4814

European-Finnish (FIN) AF: 0.438 AC: 4619 AN: 10550

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26780 AN: 67968

Other (OTH) AF: 0.328 AC: 691 AN: 2106

Alfa AF: 0.177 Hom.: 419

Bravo AF: 0.315

Asia WGS AF: 0.255 AC: 889 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.059
DANN	Benign	0.64
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9594382; hg19: chr13-32332217; COSMIC: COSV53640265;